Gabriel Torres struck twice for Panama to heap more pressure on Mexico coach Jose Manuel de la Torre.
Martinique also inflicted major shock on the opening day of the tournament as they beat Canada 1-0.
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The reputation of the Premier League means it is the most popular and one of the most watched leagues in the world.
Five English clubs will compete in the last sixteen of the Champions League for the first time ever as Liverpool, Manchester United, Manchester City, Chelsea and Tottenham face some difficult away matches.